Affinity of Rimantadine Enantiomers against Influenza A/M2 Protein Revisited

Antonios Drakopoulos, Christina Tzitzoglaki, Chulong Ma, Kathrin Freudenberger, Anja Hoffmann, Yanmei Hu, Günter Gauglitz, Michaela Schmidtke, Jun Wang, Antonios Kolocouris

Research output: Research - peer-reviewArticle

Abstract

Recent findings from solid state NMR (ssNMR) studies suggested that the (R)-enantiomer of rimantadine binds to the full M2 protein with higher affinity than the (S)-enantiomer. Intrigued by these findings, we applied functional assays, such as antiviral assay and electrophysiology (EP), to evaluate the binding affinity of rimantadine enantiomers to the M2 protein channel. Unexpectedly, no significant difference was found between the two enantiomers. Our experimental data based on the full M2 protein function were further supported by alchemical free energy calculations and isothermal titration calorimetry (ITC) allowing an evaluation of the binding affinity of rimantadine enantiomers to the M2TM pore. Both enantiomers have similar channel blockage, affinity, and antiviral potency.

LanguageEnglish (US)
Pages145-150
Number of pages6
JournalACS Medicinal Chemistry Letters
Volume8
Issue number2
DOIs
StatePublished - Feb 9 2017

Fingerprint

Rimantadine
Enantiomers
Proteins
Human Influenza
Antiviral Agents
Assays
Calorimetry
Electrophysiology
Titration
Free energy
Nuclear magnetic resonance

Keywords

  • antiviral assay
  • Bennett’s acceptance ratio
  • electrophysiology
  • free energy perturbation
  • influenza M2 pore
  • isothermal titration calorimetry
  • membrane protein
  • Rimantadine enantiomers
  • synthesis

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Cite this

Drakopoulos, A., Tzitzoglaki, C., Ma, C., Freudenberger, K., Hoffmann, A., Hu, Y., ... Kolocouris, A. (2017). Affinity of Rimantadine Enantiomers against Influenza A/M2 Protein Revisited. ACS Medicinal Chemistry Letters, 8(2), 145-150. DOI: 10.1021/acsmedchemlett.6b00311

Affinity of Rimantadine Enantiomers against Influenza A/M2 Protein Revisited. / Drakopoulos, Antonios; Tzitzoglaki, Christina; Ma, Chulong; Freudenberger, Kathrin; Hoffmann, Anja; Hu, Yanmei; Gauglitz, Günter; Schmidtke, Michaela; Wang, Jun; Kolocouris, Antonios.

In: ACS Medicinal Chemistry Letters, Vol. 8, No. 2, 09.02.2017, p. 145-150.

Research output: Research - peer-reviewArticle

Drakopoulos, A, Tzitzoglaki, C, Ma, C, Freudenberger, K, Hoffmann, A, Hu, Y, Gauglitz, G, Schmidtke, M, Wang, J & Kolocouris, A 2017, 'Affinity of Rimantadine Enantiomers against Influenza A/M2 Protein Revisited' ACS Medicinal Chemistry Letters, vol 8, no. 2, pp. 145-150. DOI: 10.1021/acsmedchemlett.6b00311
Drakopoulos A, Tzitzoglaki C, Ma C, Freudenberger K, Hoffmann A, Hu Y et al. Affinity of Rimantadine Enantiomers against Influenza A/M2 Protein Revisited. ACS Medicinal Chemistry Letters. 2017 Feb 9;8(2):145-150. Available from, DOI: 10.1021/acsmedchemlett.6b00311
Drakopoulos, Antonios ; Tzitzoglaki, Christina ; Ma, Chulong ; Freudenberger, Kathrin ; Hoffmann, Anja ; Hu, Yanmei ; Gauglitz, Günter ; Schmidtke, Michaela ; Wang, Jun ; Kolocouris, Antonios. / Affinity of Rimantadine Enantiomers against Influenza A/M2 Protein Revisited. In: ACS Medicinal Chemistry Letters. 2017 ; Vol. 8, No. 2. pp. 145-150
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